Browsing by Subject "Ischemic stroke"
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Item 4-Ethylguaiacol Modulates Neuroinflammation and Promotes Heme Oxygenase-1 Expression to Ameliorate Brain Injury in Ischemic Stroke(Frontiers Media, 2022-07-01) Weng, Wen-Tsan; Kuo, Ping-Chang; Scofield, Barbara A.; Paraiso, Hallel C.; Brown, Dennis A.; Yu, I-Chen; Yen, Jui-Hung; Microbiology and Immunology, School of MedicineIschemic stroke is caused by a sudden reduction in cerebral blood flow that subsequently induces a complex cascade of pathophysiological responses, leading to brain inflammation and irreversible infarction. 4-ethylguaiacol (4-EG) is reported to suppress inflammatory immune responses. However, whether 4-EG exerts anti-inflammatory effects in ischemic stroke remains unexplored. We evaluated the therapeutic potential of 4-EG and examined the cellular and molecular mechanisms underlying the protective effects of 4-EG in ischemic stroke. The effect of 4-EG in ischemic stroke was determined by using a transient middle cerebral artery occlusion (MCAO) animal model followed by exploring the infarct size, neurological deficits, microglia activation, inflammatory cytokine production, blood-brain barrier (BBB) disruption, brain endothelial cell adhesion molecule expression, and microglial heme oxygenase-1 (HO-1) expression. Nrf2-/- and HO-1 inhibitor ZnPP-treated mice were also subjected to MCAO to evaluate the role of the Nrf2/HO-1 pathway in 4-EG-mediated protection in ischemic stroke. We found that 4-EG attenuated infarct size and neurological deficits, and lessened BBB disruption in ischemic stroke. Further investigation revealed that 4-EG suppressed microglial activation, peripheral inflammatory immune cell infiltration, and brain endothelial cell adhesion molecule upregulation in the ischemic brain. Finally, we identified that the protective effect of 4-EG in ischemic stroke was abolished in Nrf2-/- and ZnPP-treated MCAO mice. Our results identified that 4-EG confers protection against ischemic stroke and reveal that the protective effect of 4-EG in ischemic stroke is mediated through the induction of the Nrf2/HO1 pathway. Thus, our findings suggest that 4-EG could be developed as a novel therapeutic agent for the treatment of ischemic stroke.Item A novel emergency medical services protocol to improve treatment time for large vessel occlusion strokes(PLOS, 2022-02-25) Glober , Nancy; Supples , Michael; Persaud, Sarah; Kim , David; Liao , Mark; Glidden , Michele; O'Donnell , Dan; Tainter , Christopher; Boustani , Malaz; Alexander, Andreia; Emergency Medicine, School of MedicineIn many systems, patients with large vessel occlusion (LVO) strokes experience delays in transport to thrombectomy-capable centers. This pilot study examined use of a novel emergency medical services (EMS) protocol to expedite transfer of patients with LVOs to a comprehensive stroke center (CSC). From October 1, 2020 to February 22, 2021, Indianapolis EMS piloted a protocol, in which paramedics, after transporting a patient with a possible stroke remained at the patient's bedside until released by the emergency department or neurology physician. In patients with possible LVO, EMS providers remained at the bedside until the clinical assessment and CT angiography (CTA) were complete. If indicated, the paramedics at bedside transferred the patient, via the same ambulance, to a nearby thrombectomy-capable CSC with which an automatic transfer agreement had been arranged. This five-month mixed methods study included case-control assessment of use of the protocol, number of transfers, safety during transport, and time saved in transfer compared to emergent transfers via conventional interfacility transfer agencies. In qualitative analysis EMS providers, and ED physicians and neurologists at both sending and receiving institutions, completed e-mail surveys on the process, and offered suggestions for process improvement. Responses were coded with an inductive content analysis approach. The protocol was used 42 times during the study period; four patients were found to have LVOs and were transferred to the CSC. There were no adverse events. Median time from decision-to-transfer to arrival at the CSC was 27.5 minutes (IQR 24.5-29.0), compared to 314.5 minutes (IQR 204.0-459.3) for acute non-stroke transfers during the same period. Major themes of provider impressions included: incomplete awareness of the protocol, smooth process, challenges when a stroke alert was activated after EMS left the hospital, greater involvement of EMS in patient care, and comments on communication and efficiency. This pilot study demonstrated the feasibility, safety, and efficiency of a novel approach to expedite endovascular therapy for patients with LVOs.Item Acute Ischemic Stroke, Depressed Left Ventricular Ejection Fraction, and Sinus Rhythm: Prevalence and Practice Patterns(American Heart Association, 2022) Baker, Anna D.; Schwamm, Lee H.; Sanborn, Danita Y.; Furie, Karen; Stretz, Christoph; Grory, Brian Mac; Yaghi, Shadi; Kleindorfer, Dawn; Sucharew, Heidi; Mackey, Jason; Walsh, Kyle; Flaherty, Matt; Kissela, Brett; Alwell, Kathleen; Khoury, Jane; Khatri, Pooja; Adeoye, Opeolu; Ferioli, Simona; Woo, Daniel; Martini, Sharyl; De Los Rios La Rosa, Felipe; Demel, Stacie L.; Madsen, Tracy; Star, Michael; Coleman, Elisheva; Slavin, Sabreena; Jasne, Adam; Mistry, Eva A.; Haverbusch, Mary; Merkler, Alexander E.; Kamel, Hooman; Schindler, Joseph; Sansing, Lauren H.; Faridi, Kamil F.; Sugeng, Lissa; Sheth, Kevin N.; Sharma, Richa; Neurology, School of MedicineBackground: There are limited data about the epidemiology and secondary stroke prevention strategies used for patients with depressed left ventricular ejection fraction (LVEF) and sinus rhythm following an acute ischemic stroke (AIS). We sought to describe the prevalence of LVEF ≤40% and sinus rhythm among patients with AIS and antithrombotic treatment practice in a multi-center cohort from 2002 to 2018. Methods: This was a multi-center, retrospective cohort study comprised of patients with AIS hospitalized in the Greater Cincinnati Northern Kentucky Stroke Study and 4 academic, hospital-based cohorts in the United States. A 1-stage meta-analysis of proportions was undertaken to calculate a pooled prevalence. Univariate analyses and an adjusted multivariable logistic regression model were performed to identify demographic, clinical, and echocardiographic characteristics associated with being prescribed an anticoagulant upon AIS hospitalization discharge. Results: Among 14 338 patients with AIS with documented LVEF during the stroke hospitalization, the weighted pooled prevalence of LVEF ≤40% and sinus rhythm was 5.0% (95% CI, 4.1-6.0%; I2, 84.4%). Of 524 patients with no cardiac thrombus and no prior indication for anticoagulant who survived postdischarge, 200 (38%) were discharged on anticoagulant, 289 (55%) were discharged on antiplatelet therapy only, and 35 (7%) on neither. There was heterogeneity by site in the proportion discharged with an anticoagulant (22% to 45%, P<0.0001). Cohort site and National Institutes of Health Stroke Severity scale >8 (odds ratio, 2.0 [95% CI, 1.1-3.8]) were significant, independent predictors of being discharged with an anticoagulant in an adjusted analysis. Conclusions: Nearly 5% of patients with AIS have a depressed LVEF and are in sinus rhythm. There is significant variation in the clinical practice of antithrombotic therapy prescription by site and stroke severity. Given this clinical equipoise, further study is needed to define optimal antithrombotic treatment regimens for secondary stroke prevention in this patient population.Item Association between admission haematocrit and mortality among men with acute ischaemic stroke(BMJ, 2018-04-24) Sico, Jason J.; Myers, Laura J.; Fenton, Brenda; Concato, John; Williams, Linda S.; Bravata, Dawn M.; Neurology, School of MedicineObjective: Anaemia is associated with higher mortality among patients with non-stroke cardiovascular conditions; less is known regarding the relationship between anaemia and mortality among patients with acute ischaemic stroke. Methods: Medical records were abstracted for n=3965 veterans from 131 Veterans Health Administration facilities who were admitted with ischaemic stroke in fiscal year 2007. Haematocrit values within 24 hours of admission were classified as ≤27%, 28%-32%, 33%-37%, 38%-42%, 43%-47% or ≥48%. Multivariate logistic regression was used to examine the relationship between anaemia and in-hospital, 30-day, 6-month and 1-year mortality, adjusting for age, medical comorbidities, modified Acute Physiology and Chronic Health Evaluation-III and stroke severity. Impact factors were calculated to standardise comparisons between haematocrit tier and other covariates. Results: Among n=3750 patients included in the analysis, the haematocrit values were ≤27% in 2.1% (n=78), 28%-32% in 6.2% (n=234), 33%-37% in 17.9% (n=670), 38%-42% in 36.4% (n=1366), 43%-47% in 28.2% (n=1059) and ≥48% in 9.1% (n=343). Patients with haematocrit ≤27%, compared with patients in the 38%-42% range, were more likely to have died across all follow-up intervals, with statistically significant adjusted ORs (aORs) ranging from 2.5 to 3.5. Patients with polycythaemia (ie, haematocrit ≥48%) were at increased risk of in-hospital mortality (aOR=2.9; 95% CI 1.4 to 6.0), compared with patients with mid-range admission haematocrits. Pronounced differences between patients receiving and not receiving blood transfusion limited our ability to perform a propensity analysis. Impact factors in the 1-year mortality model were 0.46 (severe anaemia), 0.06 (cancer) and 0.018 (heart disease). Conclusions: Anaemia is independently associated with an increased risk of death throughout the first year post stroke; high haematocrit is associated with early poststroke mortality. Severe anaemia is associated with 1-year mortality to a greater degree than cancer or heart disease. These data cannot address the question of whether interventions targeting anaemia might improve patient outcomes.Item Depression as a Risk Factor for Incident Ischemic Stroke Among HIV‐Positive Veterans in the Veterans Aging Cohort Study(American Heart Association, 2021-07-06) Sico, Jason J.; Kundu, Suman; So-Armah, Kaku; Gupta, Samir K.; Chang, Chung-Chou H.; Butt, Adeel A.; Gibert, Cynthia L.; Marconi, Vincent C.; Crystal, Stephen; Tindle, Hilary A.; Freiberg, Matthew S.; Stewart, Jesse C.; Medicine, School of MedicineBackground: HIV infection and depression are each associated with increased ischemic stroke risk. Whether depression is a risk factor for stroke within the HIV population is unknown. Methods and Results: We analyzed data on 106 333 (33 528 HIV-positive; 72 805 HIV-negative) people who were free of baseline cardiovascular disease from an observational cohort of HIV-positive people and matched uninfected veterans in care from April 1, 2003 through December 31, 2014. International Classification of Diseases, Ninth Revision (ICD-9) codes from medical records were used to determine baseline depression and incident stroke. Depression occurred in 19.5% of HIV-positive people. After a median of 9.2 years of follow-up, stroke rates were highest among people with both HIV and depression and lowest among those with neither condition. In Cox proportional hazard models, depression was associated with an increased risk of stroke for HIV-positive people after adjusting for sociodemographic characteristics and cerebrovascular risk factors (hazard ratio [HR], 1.18; 95% CI: 1.03-1.34; 0.014). The depression-stroke relationship was attenuated by alcohol use disorders, cocaine use, and baseline antidepressant use, and unaffected by combined antiretroviral therapy use or individual antiretroviral agents. A numerically higher HR of depression on stroke was found among those younger than 60 years. Conclusions: Depression is associated with an increased risk of stroke among HIV-positive people after adjusting for sociodemographic characteristics, traditional cerebrovascular risk factors, and HIV-specific factors. Alcohol use disorders, cocaine use, and baseline antidepressant use accounted for some of the observed stroke risk. Depression may be a novel, independent risk factor for ischemic stroke in HIV, particularly among younger people.Item Deriving Place of Residence, Modified Rankin Scale, and EuroQol-5D Scores from the Medical Record for Stroke Survivors(Karger, 2021) Sucharew, Heidi; Kleindorfer, Dawn; Khoury, Jane C.; Alwell, Kathleen; Haverbusch, Mary; Stanton, Robert; Demel, Stacie; De Los Rios La Rosa, Felipe; Ferioli, Simona; Jasne, Adam; Mistry, Eva; Moomaw, Charles J.; Mackey, Jason; Slavin, Sabreena; Star, Michael; Walsh, Kyle; Woo, Daniel; Kissela, Brett M.; Neurology, School of MedicineIntroduction: We sought to determine the feasibility and validity of estimating post-stroke outcomes using information available in the electronic medical record (EMR) through comparison with outcomes obtained from telephone interviews. Methods: The Greater Cincinnati Northern Kentucky Stroke Study is a retrospective population-based epidemiology study that ascertains hospitalized strokes in the study region. As a sub-study, we identified all ischemic stroke patients who presented to a system of 4 hospitals during the study period 1/1/2015–12/31/2015 and were discharged alive. Enrolled subjects (or proxies for cognitively-disabled patients) were contacted by telephone at 3 and 6 months post-stroke to determine current place of residence and two functional outcomes—the modified Rankin Score (mRS) and the EuroQol (EQ-5D). Concurrently, the lead study coordinator, blinded to the telephone assessment outcomes, reviewed all available EMRs to estimate outcome status. Agreement between outcomes estimated from the EMR with “gold-standard” data obtained from telephone interviews was analyzed using the kappa statistic or interclass correlation (ICC), as appropriate. For each outcome, EMR-determined results were evaluated for added value beyond the information readily available from the stroke hospital stay. Results: Of 381 ischemic strokes identified, 294 (median [IQR] age 70 [60–79] years, 4% black, 52% female) were interviewed post-stroke. Agreement between EMR and telephone for 3-month residence was very good (kappa=0.84, 95% CI 0.74–0.94), good for mRS (weighted kappa=0.75, 95% CI 0.70–0.80), and good for EQ-5D (ICC=0.74, 95% CI 0.68–0.79). Similar results were observed at 6 months post stroke. At both 3 and 6 months post stroke, EMR-determined outcomes added value in predicting the gold standard telephone results beyond the information available from the stroke hospitalization; the added fraction of new information ranged from 0.25 to 0.59. Conclusions: Determining place of residence, mRS, and EQ-5D outcomes derived from information recorded in the EMR post-stroke, without patient contact, is feasible and has good agreement with data obtained from direct contact. However, we note that the level of agreement for mRS and EQ-5D was higher for proxy interviews and that the EMR often reflects health care providers’ judgments that tend to overestimate disability and underestimate quality of life.Item Development, Validation, and Assessment of an Ischemic Stroke or Transient Ischemic Attack-Specific Prediction Tool for Obstructive Sleep Apnea(Elsevier, 2017-08) Sico, Jason J.; Yaggi, H. Klar; Ofner, Susan; Concato, John; Austin, Charles; Ferguson, Jared; Qin, Li; Tobias, Lauren; Taylor, Stanley; Vaz Fragoso, Carlos A.; McLain, Vincent; Williams, Linda S.; Bravata, Dawn M.; Biostatistics, School of Public HealthBACKGROUND: Screening instruments for obstructive sleep apnea (OSA), as used routinely to guide clinicians regarding patient referral for polysomnography (PSG), rely heavily on symptomatology. We sought to develop and validate a cerebrovascular disease-specific OSA prediction model less reliant on symptomatology, and to compare its performance with commonly used screening instruments within a population with ischemic stroke or transient ischemic attack (TIA). METHODS: Using data on demographic factors, anthropometric measurements, medical history, stroke severity, sleep questionnaires, and PSG from 2 independently derived, multisite, randomized trials that enrolled patients with stroke or TIA, we developed and validated a model to predict the presence of OSA (i.e., Apnea-Hypopnea Index ≥5 events per hour). Model performance was compared with that of the Berlin Questionnaire, Epworth Sleepiness Scale (ESS), the Snoring, Tiredness, Observed apnea, high blood Pressure, Body mass index, Age, Neck circumference, and Gender instrument, and the Sleep Apnea Clinical Score. RESULTS: The new SLEEP Inventory (Sex, Left heart failure, ESS, Enlarged neck, weight [in Pounds], Insulin resistance/diabetes, and National Institutes of Health Stroke Scale) performed modestly better than other instruments in identifying patients with OSA, showing reasonable discrimination in the development (c-statistic .732) and validation (c-statistic .731) study populations, and having the highest negative predictive value of all in struments. CONCLUSIONS: Clinicians should be aware of these limitations in OSA screening instruments when making decisions about referral for PSG. The high negative predictive value of the SLEEP INventory may be useful in determining and prioritizing patients with stroke or TIA least in need of overnight PSG.Item Editorial: Ischemic stroke as systemic disorder involving both nervous and immune systems(Frontiers Media, 2023-05-10) Liu, Qingkun; Wang, Yan; Yen, Jui-Hung Jimmy; Microbiology and Immunology, School of MedicineItem Hospital Factors, Performance on Process Measures After Transient Ischemic Attack, and 90-Day Ischemic Stroke Incidence(American Heart Association, 2021) Levine, Deborah A.; Perkins, Anthony J.; Sico, Jason J.; Myers, Laura J.; Phipps, Michael S.; Zhang, Ying; Bravata, Dawn M.; Biostatistics, School of Public HealthBackground and purpose: We determined the association between hospital factors, performance on transient ischemic attack (TIA) process measures, and 90-day ischemic stroke incidence. Methods: Longitudinal analysis of retrospectively obtained data on 9168 veterans ≥18 years with TIA presenting to the emergency department or inpatient unit at 69 Veterans Affairs hospitals with ≥10 eligible patients per year in fiscal years 2015 to 2018. Process measures were high/moderate potency statin within 7 days of discharge, antithrombotic by day 2, and hypertension control (<140/90 mm Hg) at 90 days. The outcome was 90-day stroke incidence. Results: During the 4-year study period, hospitals significantly increased statin use (adjusted odds ratio [aOR] per 1-year increase, 1.24 [95% CI, 1.17–1.32]; P<0.001), whereas neither hypertension control (P=0.44) nor antithrombotic use (P=0.82) improved over time. Hospitals that admitted a higher proportion of TIA patients versus emergency department discharge had significantly greater use of statins (aOR per 10-percentage point increase in the proportion of TIA patients admitted, 1.09 [1.03–1.16]; P=0.003) and antithrombotics (aOR per 10-percentage point increase in TIA patients admitted, 1.14 [1.06–1.23]; P<0.001). Hospitals with higher emergency physician staffing and lower TIA patient volume had greater use of antithrombotics (aOR per 1 full-time physician increase, 1.05 [1.01–1.08]; P=0.008 and aOR per 10-patient decrease in volume, 1.09 [1.01–1.16]; P=0.02). Higher emergency physician staffing was associated with lower 90-day stroke incidence (aOR per 1 full-time physician increase, 0.96 [0.92–0.99]; P=0.02) but other hospital factors were not. Conclusions: Hospitals admitting higher percentages of TIA patients and having higher emergency physician staffing have greater performance on select guideline-concordant process measures for TIA. Higher emergency physician staffing was associated with improved outcomes 90 days after TIA.Item In-hospital outcomes and 30-day readmission rates among ischemic and hemorrhagic stroke patients with delirium(PLOS, 2019-11-14) Vahidy, Farhaan S.; Bambhroliya, Arvind B.; Meeks, Jennifer R.; Rahman, Omar; Ely, E. Wesley; Slooter, Arjen J. C.; Tyson, Jon E.; Miller, Charles C.; McCullough, Louise D.; Savitz, Sean I.; Khan, Babar; Medicine, School of MedicineOBJECTIVE: Delirium is associated with poor outcomes among critically ill patients. However, it is not well characterized among patients with ischemic or hemorrhagic stroke (IS and HS). We provide the population-level frequency of in-hospital delirium and assess its association with in-hospital outcomes and with 30-day readmission among IS and HS patients. METHODS: We analyzed Nationwide in-hospital and readmission data for years 2010-2015 and identified stroke patients using ICD-9 codes. Delirium was identified using validated algorithms. Outcomes were in-hospital mortality, length of stay, unfavorable discharge disposition, and 30-day readmission. We used survey design logistic regression methods to provide national estimates of proportions and 95% confidence intervals (CI) for delirium, and odds ratios (OR) for association between delirium and poor outcomes. RESULTS: We identified 3,107,437 stroke discharges of whom 7.45% were coded to have delirium. This proportion significantly increased between 2010 (6.3%) and 2015 (8.7%) (aOR, 95% CI: 1.04, 1.03-1.05). Delirium proportion was higher among HS patients (ICH: 10.0%, SAH: 9.8%) as compared to IS patients (7.0%). Delirious stroke patients had higher in-hospital mortality (12.3% vs. 7.8%), longer in-hospital stay (11.6 days vs. 7.3 days) and a significantly greater adjusted risk of 30-day-readmission (16.7%) as compared to those without delirium (12.2%) (aRR, 95% CI: 1.13, 1.11-1.15). Upon readmission, patients with delirium at initial admission continued to have a longer length of stay (7.7 days vs. 6.6 days) and a higher in-hospital mortality (9.3% vs. 6.4%). CONCLUSION: Delirium identified through claims data in stroke patients is independently associated with poor in-hospital outcomes both at index admission and readmission. Identification and management of delirium among stroke patients provides an opportunity to improve outcomes.